Flavin-dependent N-hydroxylating enzymes: Distribution and application

Carolin Mügge, Thomas Heine, Alvaro Gomez Baraibar, Willem J.H. van Berkel, Caroline E. Paul, Dirk Tischler*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)
18 Downloads (Pure)

Abstract

Amino groups derived from naturally abundant amino acids or (di)amines can be used as “shuttles” in nature for oxygen transfer to provide intermediates or products comprising N-O functional groups such as N-hydroxy, oxazine, isoxazolidine, nitro, nitrone, oxime, C-, S-, or N-nitroso, and azoxy units. To this end, molecular oxygen is activated by flavin, heme, or metal cofactor-containing enzymes and transferred to initially obtain N-hydroxy compounds, which can be further functionalized. In this review, we focus on flavin-dependent N-hydroxylating enzymes, which play a major role in the production of secondary metabolites, such as siderophores or antimicrobial agents. Flavoprotein monooxygenases of higher organisms (among others, in humans) can interact with nitrogen-bearing secondary metabolites or are relevant with respect to detoxification metabolism and are thus of importance to understand potential medical applications. Many enzymes that catalyze N-hydroxylation reactions have specific substrate scopes and others are rather relaxed. The subsequent conversion towards various N-O or N-N comprising molecules is also described. Overall, flavin-dependent N-hydroxylating enzymes can accept amines, diamines, amino acids, amino sugars, and amino aromatic compounds and thus provide access to versatile families of compounds containing the N-O motif. Natural roles as well as synthetic applications are highlighted.• N-O and N-N comprising natural and (semi)synthetic products are highlighted.• Flavin-based NMOs with respect to mechanism, structure, and phylogeny are reviewed.• Applications in natural product formation and synthetic approaches are provided. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)6481-6499
Number of pages19
JournalApplied Microbiology and Biotechnology
Volume104
Issue number15
DOIs
Publication statusPublished - 2020

Keywords

  • Bioactive compounds
  • Biocatalysis
  • Biotransformation
  • Flavoproteins
  • Monooxygenases
  • N-Hydroxylases
  • Phylogenetics
  • Siderophores

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